title: Beyond patient reported pain: perfusion magnetic resonance imaging demonstrates reproducible cerebral representation of ongoing post-surgical pain.
abstract: Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Kings College London, London, United Kingdom. Matthew.Howard@kcl.ac.uk
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Howard
authors.forename: Kristina
authors.initials: K
authors.lastname: Krause
authors.forename: Nadine
authors.initials: N
authors.lastname: Khawaja
authors.forename: Nathalie
authors.initials: N
authors.lastname: Massat
authors.forename: Fernando
authors.initials: F
authors.lastname: Zelaya
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.forename: John P
authors.initials: JP
authors.lastname: Huggins
authors.forename: William
authors.initials: W
authors.lastname: Vennart
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Tara F
authors.initials: TF
authors.lastname: Renton
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000502:physiology; D018592:Cross-Over Studies; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D008964:Molar, Third / Q000601:surgery; D019647:Oral Surgical Procedures / Q000009:adverse effects / Q000534:rehabilitation; D056948:Orthognathic Surgical Procedures; D010147:Pain Measurement / Q000379:methods* / Q000639:trends*; D010149:Postoperative Pain / Q000175:diagnosis* / Q000503:physiopathology; D011182:Postoperative Care / Q000379:methods / Q000639:trends; D011184:Postoperative Period; D012649:Self Concept; D057566:Self Report; D055815:Young Adult